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IL-12 is required for differentiation of pathogenic CD8+ T cell effectors that cause myocarditis
Nir Grabie, … , Jonathan G. Seidman, Andrew H. Lichtman
Nir Grabie, … , Jonathan G. Seidman, Andrew H. Lichtman
Published March 1, 2003
Citation Information: J Clin Invest. 2003;111(5):671-680. https://doi.org/10.1172/JCI16867.
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Article Autoimmunity Article has an altmetric score of 1

IL-12 is required for differentiation of pathogenic CD8+ T cell effectors that cause myocarditis

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Abstract

Cardiac antigen–specific CD8+ T cells are involved in the autoimmune component of human myocarditis. Here, we studied the differentiation and migration of pathogenic CD8+ T cell effector cells in a new mouse model of autoimmune myocarditis. A transgenic mouse line was derived that expresses cardiac myocyte restricted membrane-bound ovalbumin (CMy-mOva). The endogenous adaptive immune system of CMy-mOva mice displays tolerance to ovalbumin. Adoptive transfer of naive CD8+ T cells from the ovalbumin-specific T cell receptor–transgenic (TCR-transgenic) OT-I strain induces myocarditis in CMy-mOva mice only after subsequent inoculation with ovalbumin-expressing vesicular stomatitis virus (VSV-Ova). OT-I effector T cells derived in vitro in the presence or absence of IL-12 were adoptively transferred into CMy-mOva mice, and the consequences were compared. Although IL-12 was not required for the generation of cytolytic and IFN-γ–producing effector T cells, only effectors primed in the presence of IL-12 infiltrated CMy-mOva hearts in significant numbers, causing lethal myocarditis. Furthermore, analysis of OT-I effectors collected from a mediastinal draining lymph node indicated that only effectors primed in vitro in the presence of IL-12 proliferated in vivo. These data demonstrate the importance of IL-12 in the differentiation of pathogenic CD8+ T cells that can cause myocarditis.

Authors

Nir Grabie, Michael W. Delfs, Jason R. Westrich, Victoria A. Love, George Stavrakis, Ferhaan Ahmad, Christine E. Seidman, Jonathan G. Seidman, Andrew H. Lichtman

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Activation of naive OT-I T cells in CMy-mOva mice by VSV-Ova inoculation

Activation of naive OT-I T cells in CMy-mOva mice by VSV-Ova inoculation


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ISSN: 0021-9738 (print), 1558-8238 (online)

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